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Biomedical subjects

L D Miller

Publications and source records attributed to L D Miller.

At least 19 recordsLinked to original sources

Transcription patterning of uncoupled proliferation and differentiation in myelodysplastic bone marrow with erythroid-focused arrays.

Because abnormal erythroid differentiation is the most common manifestation of the myelodysplastic syndromes (MDS), it was hypothesized that erythroid gene expression may be used to illustrate myelodysplastic transcription patterns. Ten normal bone marrow aspirates (NBM) were first analyzed using an erythroid-focused cDNA array to define steady-state transcription levels. Proliferation and differentiation gene subsets were identified by statistically significant differences between NBM and erythroleukemia gene expression. Next, cDNAs from 5 separate MDS aspirates were studied: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation (RAEB-T), and RAEB-T/secondary MDS. A distinct pattern of significantly increased proliferation-associated and reduced differentiation-associated gene activity was established for MDS.

Aged↗

Surfactant proteins and cell markers in the respiratory epithelium of the amphibian, Ambystoma mexicanum.

The respiratory tract is lined by diverse epithelial cell types whose morphology, gene expression and functions are highly specialized along the cephalo-caudal axis of the lung. Pulmonary gas exchange, surface tension reduction, host defense, fluid and electrolyte transport are functions shared by various vertebrate species, each organism facing similar requirements for adaptation to air breathing. Consistent with this concept, we have identified distinct respiratory epithelial cell populations in the amphibian, Ambystoma mexicanum, using morphologic, histochemical and immunochemical techniques. Thyroid transcription factor-1 (TTF-1), a homeodomain nuclear transcription factor critical to lung formation, and surfactant protein B (SP-B), an amphipathic polypeptide required for surfactant function, were detected in the peripheral respiratory epithelial cells of the axolotl lung, in cells with characteristics of Type II alveolar epithelial cells in mammals. beta-Tubulin and carbohydrate staining identified distinct subsets of ciliated and goblet cells. SP-D, a member of the collectin family of innate host defense proteins, was also detected in peripheral epithelial cells of the axolotl lung. Pulmonary surfactant and host defense proteins are shared across diverse phyla supporting the concept that pulmonary structure and function have evolved from common ancestors.

Ambystoma mexicanum↗

Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation.

To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the beta-catenin-T-cell factor complex. This was confirmed biochemically, as beta-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a beta-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.

Animals↗

High-fidelity mRNA amplification for gene profiling.

The completion of the Human Genome Project has made possible the comprehensive analysis of gene expression, and cDNA microarrays are now being employed for expression analysis in cancer cell lines or excised surgical specimens. However, broader application of cDNA microarrays is limited by the amount of RNA required: 50-200 microg of total RNA (T-RNA) and 2-5 microg poly(A) RNA. To broaden the use of cDNA microarrays, some methods aiming at intensifying fluorescence signal have resulted in modest improvement. Methods devoted to amplifying starting poly(A) RNA or cDNA show promise, in that detection can be increased by orders of magnitude. However, despite the common use of these amplification procedures, no systematic assessment of their limits and biases has been documented. We devised a procedure that optimizes amplification of low-abundance RNA samples by combining antisense RNA (aRNA) amplification with a template-switching effect (Clonetech, Palo Alto, CA). The fidelity of aRNA amplified from 1:10,000 to 1:100,000 of commonly used input RNA was comparable to expression profiles observed with conventional poly(A) RNA- or T-RNA-based arrays.

Gene Amplification↗

Gamma hydroxybutyric acid (GHB): an increasing trend in drug abuse.

The use of recreational drugs in society is becoming a widespread problem increasing the workload of all the emergency services. Gamma hydroxybutyric acid (GHB) is one of these, a drug used primarily for its euphoric effect. Toxic effects of ingestion include bradycardia, slow respiration or apnoea, coma and death. We present seven cases, all of which had consumed GHB either alone or in conjunction with other drugs and alcohol. The presentation, clinical features and management of these cases are described. All health care personnel involved in the emergency setting need to know of its existence, toxic effects and initial management with particular reference to airway control and possible assisted ventilation.

Adolescent↗

Experimental Brucella abortus induced abortion in a llama: pathologic effects.

Brucella abortus infection has not been documented in llamas. This report describes the abortion of the only pregnant animal in a group of 12. The llama was infected by inoculating 1 x 10(8) viable B. abortus organisms into the conjunctival sac. Forty-three days postinfection, the llama aborted a fetus of approximately 8 months gestational age. Brucella organisms were isolated from the placenta and all fetal specimens examined. These organisms were also isolated from the dam's mammary gland and numerous lymph nodes when the llama was necropsied 42 days later. Microscopically, there was a moderate, multifocal, lymphocytic and histiocytic, subacute placentitis with marked loss of trophoblastic epithelial cells. The superficial chorioallantoic stroma contained abundant necrotic and mineralized debris as well as numerous swollen capillaries protruding multifocally from the denuded surface. Immunohistochemistry revealed that these capillaries, as well as sloughed and intact trophoblasts, were expanded by large numbers of Brucella organisms. Brucellar antigen was also detected in occasional macrophages in the fetal kidney and lung. Ultrastructurally, bacteria labeled by an antibody-based colloidal gold procedure were located within degenerate capillaries, within necrotic leukocytes, and extracellularly in the placental stroma.

Abortion, Veterinary↗

Prothrombin Greenville, Arg517-->Gln, identified in an individual heterozygous for dysprothrombinemia.

A 64-year-old white male was referred for evaluation of prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) obtained before elective surgery with initial PT and PTT results of 14.9 and 38.4 seconds, respectively, which corrected to normal in 1:1 mixes with normal plasma. Functional prothrombin assay indicated a level of 51% with thromboplastin as an activator. The prothrombin antigen was 102%. This discordance in the functional and immunologic prothrombin levels was evidence for dysprothrombinemia. Western blotting showed that thrombin was formed at a normal rate in diluted plasma consistent with a mutation within the thrombin portion of prothrombin. DNA was isolated from leukocytes and the thrombin exons were amplified by polymerase chain reaction, cloned, and sequenced. For exon 13, eight clones were sequenced with four clones showing a point mutation in the codon for Arg517, which would result in substitution by Gln. Arg517 is part of the Arg-Gly-Asp(RGD) sequence in thrombin and contributes to an ion cluster with aspartic acid residues 552 and 554. Mutation at this residue most probably distorts the structure of the Na+ binding site in thrombin. This is the first report indicating the critical role of Arg517 in the normal physiological interaction of thrombin with fibrinogen. This dysprothrombin is designated Prothrombin Greenville.

Arginine↗

Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors.

OBJECTIVE: Prophylactic therapies have demonstrated efficacy in reducing the incidence of deep venous thrombosis (DVT) in neurosurgical patients. Retrospective analysis of patients undergoing neurosurgical procedures at the University of Michigan demonstrated a high incidence (14%) of postoperative DVT among patients with intracranial neoplasms treated with sequential compression device (SCD) prophylaxis alone. Therefore, we investigated the efficacy and safety of the low-molecular weight heparin enoxaparin in preventing DVT in patients with brain tumors. The goal of the study was to compare SCD, enoxaparin, and combined SCD/enoxaparin prophylaxis among patients requiring surgery for treatment of intracranial neoplasms. METHODS: Eligible patients were randomized to SCD, enoxaparin, or combined therapy. Treatment was initiated before the induction of anesthesia and was continued throughout the hospital stay. Patients were screened for DVT, using duplex imaging, on four occasions in the first 1 month after surgery. The incidences of DVT and serious adverse events were compared between groups using analysis of variance and the Dunnet two-sided t test. RESULTS: Sixty-eight patients completed the study. Postoperative DVT occurred in 3 of 22 (13.6%) SCD-treated patients, 1 of 23 (4.3%) enoxaparin-treated patients, and 4 of 23 (17.4%) SCD/enoxaparin-treated patients. Differences were not statistically significant. Postoperative intracranial hemorrhage did not occur in patients in the SCD-treated group, whereas 5 of 46 patients receiving low-molecular weight heparin suffered clinically significant intracranial hemorrhage. The study was terminated because of the increased incidence of adverse events in the enoxaparin-treated groups. CONCLUSION: Enoxaparin therapy initiated at the time of anesthesia induction increases postoperative intracranial hemorrhage.

Adult↗

Effects of the program-management model: a case study on professional rehabilitation nursing.

In an attempt to increase organizational innovation and flexibility, Cardinal Hill Rehabilitation Hospital moved from the traditional discipline-management model to the program-management model. In the restructuring, the integrity of professional nursing practices was put to the test when the director of nursing position and numerous staff nursing positions were eliminated. This article evaluates statistics from the three years that have elapsed since the restructuring event in order to determine the new program-management model's compatibility with patient outcomes associated with professional nursing standards.

Disease Management↗

Internal fixation of the spine using a braided titanium cable: clinical results and postoperative magnetic resonance imaging.

Segmental spinal fixation using sublaminar or interspinous stainless steel wire has been successfully used for many years. Stainless steel cables have been developed that are stronger and more flexible, allowing for shorter operative time and decreased risk of neurological deficit. However, stainless steel implants create significant artifact on magnetic resonance imaging (MRI), reducing the postoperative usefulness of this imaging modality. Titanium instrumentation has the advantage of producing minimal MRI artifact. Recently, a braided titanium cable has been developed that has the advantages of strength and flexibility as well as minimal production of MRI artifact. We present a series of 50 patients who underwent internal fixation of the spine using a braided titanium cable either alone or in combination with supplementary titanium instrumentation. No instrument failures have occurred to date. Postoperative MRI scans have revealed minimal implant-related artifact, allowing for high-resolution, noninvasive postoperative imaging of the neuraxis. We conclude that braided titanium cable has significant advantages over stainless steel cable or monofilament wire and is a valuable instrument for segmental spine fixation.

Adolescent↗

An atypical T-cell lymphosarcoma in a calf with bovine immunodeficiency-like virus infection.

An 11-month-old Holstein calf experimentally infected with bovine immunodeficiency-like virus (BIV) developed T-cell lymphosarcoma 5 months postinoculation, concurrent with progressive monocytosis. Tumors were found in the thymus, multiple lymph nodes, and brain. Tumor cells were CD2+, CD4-, CD8-T cells. Infectious BIV could be recovered from splenic tissue and blood mononuclear cells. Bovine leukemia virus was not present. Because this calf was part of an ongoing experiment on the pathogenesis of BIV infection, immune function data were also available both before and after lymphosarcoma developed. Neutrophil and monocyte function were normal, but lymphocyte blastogenesis was enhanced before the development of lymphosarcoma. Follicular hyperplasia in lymphoid tissues was also seen. This case raises the possibility that BIV infection may cause or be associated with some cases of atypical T-cell lymphosarcoma, without evidence of immune suppression at the time of tumor onset.

Animals↗

A multisite study of client outcomes in assertive community treatment.

OBJECTIVE: This study examined outcomes of clients admitted to assertive community treatment programs simultaneously implemented at six sites in northeastern Indiana. METHODS: A total of 212 clients at risk for psychiatric rehospitalization were assessed at baseline and at six-month intervals for 18 months after admission to assertive community treatment programs. Data on rehospitalization, quality of life, and level of functioning were compared using t tests. Progressive improvement was also examined by linear trend analysis. RESULTS: Frequency of psychiatric hospitalization was reduced by one-third and the number of inpatient days by 50 percent after admission to the program. Improvements were progressive, with continued reductions over the 18-month period. Progressive improvements also occurred in quality of life as measured by both client and staff ratings. Case managers rated clients as having improved family and social support, increased self-reliance and independence, and improved daily living skills. Clients reported significantly more legal problems, which may have been an artifact of increased monitoring during treatment. A key element of the programs' success was the position of clinical coordinator, important functions of which are described. CONCLUSIONS: Results of this study provide support for wide-scale dissemination of assertive community treatment as an effective form of community care for persons with serious mental illness.

Activities of Daily Living↗

Immunohistochemical identification of porcine reproductive and respiratory syndrome virus (PRRSV) antigen in the heart and lymphoid system of three-week-old colostrum-deprived pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) antigens were detected by a streptavidin-biotin complex technique in tissues of 3-week-old colostrum-deprived pigs that had been inoculated intranasally with PRRSV and had developed moderate respiratory disease. Moderate, multifocal, tan-colored consolidation of the lungs and severe enlargement of the lymph nodes were noted at necropsy. Severe interstitial pneumonia characterized by type 2 pneumocyte proliferation, septal infiltration with mononuclear cells, and accumulation of macrophages and necrotic cells in alveolar spaces was observed at 4 and 9 days postinoculation. Moderate multifocal perivascular lymphohistiocytic myocarditis was observed at 9 days postinoculation. Marked lymphoid follicular hyperplasia and follicular necrosis in the tonsil, spleen, and lymph nodes was observed. A monoclonal antibody that recognizes a conserved epitope of PRRSV nucleocapsid protein was used as primary antibody for immunohistochemistry. Antigen was readily detected in alveolar macrophages in the lung and in endothelial cells and macrophages in the heart. Macrophages and cells resembling dendritic cells in tonsil, lymph nodes, thymus, and spleen also stained intensely positive for viral antigen. PRRSV appears to replicate primarily within macrophages in the respiratory and lymphoid systems of the pig.

Animals↗

Canine distemper epizootic in lions, tigers, and leopards in North America.

Canine distemper virus (CDV) infection occurred in captive leopards (Panthera pardus), tigers (Panthera tigris), lions (Panthera leo), and a jaguar (Panthera onca) in 1991 and 1992. An epizootic affected all 4 types of cats at the Wildlife Waystation, San Fernando, California, with 17 mortalities. CDV-infected raccoons were thought to be the source of infection in these cats. Two black leopards died at the Naibi Zoo, Coal Valley, Illinois, and 2 tigers died at the Shambala Preserve, Acton, California. Initial clinical signs were anorexia with gastrointestinal and/or respiratory disease followed by seizures. Canine distemper virus was isolated from 3 leopards, 3 tigers, and 3 lions that died or were euthanized when moribund. Monoclonal antibody testing identified the virus isolates as CDV. Gross and histopathologic findings were similar to those found in canids with distemper with a few exceptions. There were fewer lesions in the brain, and there was a pronounced type 2 cell proliferation in the lung, with inclusion bodies and CDV antigen demonstrated by immunohistology. Neutralizing antibody to CDV was found in high titers in serum from most animals but was absent or was found only in low titers in some cats that succumbed after CDV infection. There was a marked difference in neutralizing antibody titers when tests were done with different strains of CDV.

Animals↗

An indirect microimmunofluorescence test for detection of chlamydial antibodies in ovine fetal fluids.

The objective of this study was to evaluate an indirect microimmunofluorescence test (IMIF) for detection of chlamydial antibodies in serum and/or thoracic fluids of aborted ovine fetuses. One hundred eighty-two ovine fetuses, including 64 fetuses from 40 ewes that were experimentally infected with an ovine abortion strain of Chlamydia psittaci at gestation days 90-100, 10 fetuses from 6 normal ewes, and 108 fetuses selected from those received at the Iowa Veterinary Diagnostic Laboratory, were evaluated in this study. Fetuses from experimentally infected ewes were examined 4-60 days after inoculation. The IMIF findings were compared with the results of complement fixation serology for chlamydiae and concentrations of immunoglobulin (IgG). Chlamydiae-specific antibodies were detected by IMIF in 28 of 38 fetuses infected with C. psittaci. Elevated levels of IgG and IMIF titers > or = 1:8 were consistent findings in ovine fetuses infected with chlamydiae for more than 24 days. IgG levels and titers of chlamydial antibodies increased with maturity of the fetus and duration of chlamydial infection. Chlamydial antibodies were not detected with the complement fixation test. Fluids from ovine fetuses aborted as a result of other causes also were examined, and IMIF results were negative. The results of this study indicate that the IMIF is a useful and relatively rapid test for identification of chlamydial antibodies in ovine fetuses.

Abortion, Veterinary↗

Surveillance for lesions of bovine spongiform encephalopathy in U.S. cattle.

The appearance of bovine spongiform encephalopathy (BSE) as a new disease of cattle in 1985-1987 increased worldwide interest in various aspects of human and animal spongiform encephalopathies. In the United States, a part of the surveillance effort has been directed toward prospective examination of bovine brain specimens for lesions of BSE. One focus area has been to obtain specimens from cattle that (1) are two years of age or older, (2) have documented signs of neurologic disease, and (3) have received protein supplement as a substantial part of the i.v. ration. Another focus area has been to examine rabies-suspect cases that were rabies-negative. A third area has been to obtain the results of bovine neuropathology examinations being conducted at other state and regional laboratories. Specimens have been obtained by direct submission and by referral from other public health and veterinary diagnostic laboratories. Many of the cases have been classified as having (1) inflammatory lesions such as listeriosis, pseudorabies, brain abscesses and inflammation of undetermined cause, (2) degenerative lesions such as polio-encephalomalacia, lead poisoning, Wallerian degeneration, siderocalcinosis, and lipofuscinosis, (3) neoplastic lesions such as meningioma and Schwannoma, and (4) no significant findings. Other case results were reported as inflammation or no significant findings. Of the 459 cases reported here none has contained lesions with the characteristics and distribution typical of BSE.

Animals↗